The significance of persistent viral infections in the genesis of chronic disease in man and animals is of increasing concern to persons in biomedical research. One distinctive group of such infections is represented by the so-called slow viral diseases of domestic animals. They have been of prime importance as naturally occurring models for studying the unusual host-virus interactions resulting in protracted disease after a long incubation period. The main purpose of this project is to gain an insight into the natural history and pathogenesis of these diseases. Of less immediate concern is detailed characterization of the heterogeneous group of causative viruses. Standard methods of virology, pathology, serology, and immunology are used to elucidate the underlying biologic phenomena in scrapie of sheep, a similar polioencephalopathy of mink, Aleutian disease of mink, and progressive pneumonia of sheep. Most attention has been directed to obtaining data on the virologic and immunologic events that occur in each disease.